Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex
Articolo
Data di Pubblicazione:
2015
Abstract:
NMDA receptor (NMDAR) composition and synaptic retention represent pivotal features in the physiology and pathology of excitatory synapses. Here, we identify Rabphilin 3A (Rph3A) as a new GluN2A subunit-binding partner. Rph3A is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites. We find that Rph3A is enriched at dendritic spines. Protein-protein interaction assays reveals that Rph3A N-terminal domain interacts with GluN2A(1349-1389) as well as with PSD-95(PDZ3) domains, creating a ternary complex. Rph3A silencing in neurons reduces the surface localization of synaptic GluN2A and NMDAR currents. Moreover, perturbing GluN2A/Rph3A interaction with interfering peptides in organotypic slices or in vivo induces a decrease of the amplitude of NMDAR-mediated currents and GluN2A density at dendritic spines. In conclusion, Rph3A interacts with GluN2A and PSD-95 forming a complex that regulates NMDARs stabilization at postsynaptic membranes.
Tipologia CRIS:
03A-Articolo su Rivista
Elenco autori:
Stanic, Jennifer; Carta, Mario; Eberini, Ivano; Pelucchi, Silvia; Marcello, Elena; GENAZZANI, Armando; Racca, Claudia; Mulle, Christophe; Di Luca, Monica; Gardoni, Fabrizio
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